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Background: A simultaneous integrated boost (SIB) may result in increased out-of-field (D OOF ) and photoneutron (H PN ) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare D OOF and H PN in flattened (FLAT) and flattening filter-free (FFF) 6‑MV and 10-MV VMAT treatment plans with and without SIB., Methods: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured D OOF and H PN in 61.8 cm distance from the isocenter. The 6‑ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size A eq . Pearson's correlation coefficients between the presented quantities were determined., Results: The SIB plans resulted in decreased H PN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less H PN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased D OOF likewise by 39% for all given scenarios, while the FFF mode reduced D OOF on average by 60%. A strong Pearson correlation was found between MU and H PN (r > 0.9) as well as D OOF (0.7 < r < 0.9)., Conclusion: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6‑MV SIB FFF-VMAT when considering photoneutron or OOF doses., (© 2023. The Author(s).)

Purpose: Stereotactic radiosurgery with linear accelerators (LINACs) or Leksell Gamma Knife® (LGK, Elekta AB) is an established treatment option for intracranial tumors. When those are involving/abutting organs at risk (OAR), homogenous and normofractionated treatments outmatch single fraction deliveries. In such situations, it would be desirable to balance LINAC's homogeneity benefits with LGK's dose gradient attributes. In this study, we determined homogeneity and OAR sparing ranges using a non-clinical, homogenous prototype version of LGK Lightning., Methods: We retrospectively analyzed thirty fractionated LGK Icon in-house patients with acoustic neuromas, pituitary adenomas and meningiomas. Four treatment plans were generated (54 Gy,1.8 Gy/fx) per patient: one LINAC plan, one clinical Lightning plan ("LGK") and two prototype Lightning plans ("LGK Hom" and "LGK OAR"). We analyzed D mean and D 2% for different OAR, Gradient Index (GI), Paddick Conformity Index (PCI), Homogeneity Index (HI) and beam-on-time (BOT)., Results: While the LINAC vs. Lightning plans (LGK Hom|LGK OAR|LGK) boast better homogeneity (median: 1.08 vs. 1.18|1.24|1.35) and shorter BOT (median: 137 s vs. 432 s|510 s|510 s), Lightning plans show improved GI (median: 6.68 vs. 3.86|3.50|3.19), similar PCI (median: 0.75 vs. 0.76|0.75|0.82) and significantly reduced OAR doses. For in-tumor OAR, LGK Hom and LINAC plans achieves similar OAR sparing with improved GI for LGK Hom., Conclusions: This study is a preliminary attempt to combine the dosimetric advantages of LINAC and LGK treatment planning. We observed that LGK plan homogeneity can be improved toward LINAC standards while maintaining the LGK advantage of favorable OAR doses and GI. Additionally, in-tumor OAR hotspots can be considerably reduced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics., Methods: Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT 1 ) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT 2-n ) (IGRT scenario). Two additional TPs were generated on sCT 2-n : one minimizing the lung-dose while preserving the D 95% (PTV) (isoeffective scenario), the other escalating the D 95% (PTV) with a constant V 20Gy (lung ipsilateral ) (isotoxic scenario)., Results: Compared to the original TPs predicted dose, the median D 95% (PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V 20Gy (lung ipsilateral ) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V 20Gy (lung ipsilateral ) by 3.1% ± 3.6%. Furthermore, the median V 5% (heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V 20Gy (lung ipsilateral ) and V 5% (heart) was feasible., Conclusions: We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials., (© 2023. The Author(s).)

Purpose: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial., Methods and Materials: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established., Results: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V 14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome., Conclusions: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques., Methods and Materials: A multiparametric specification of target dose (gross target volume [GTV] D50% , GTV D0.1cc , GTV V90% , planning target volume [PTV] V70% ) with a prescription dose of GTV D50%  = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTV Dmin , PTV D98% , PTV D2% , PTV Dmax ). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons., Results: GTV D50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for D max , PTV D98% , GTV D98% , and PTV Dmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTV D50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTV Dmax , PTV D98% , PTV D2% , and PTV Dmin prescription. Deviations were significant for all combinations but for the PTV Dmax prescription compared with GTV D50% and PTV D98% . Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTV D50% and PTV D98% prescription showed the least difference between the systems., Conclusions: This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A long-standing hypothesis in radiotherapy is that intensity-modulated radiotherapy (IMRT) increases the risk of second cancer due to low-dose exposure of large volumes of normal tissue. Therefore, young patients are still treated with conventional techniques rather than with modern IMRT. We challenged this hypothesis in first-of-its-kind experiments using an animal model. Cancer-prone Tp53 +/C273X knockout rats received mediastinal irradiation with 3 × 5 or 3 × 8 Gy using volumetric-modulated arc therapy (VMAT, an advanced IMRT) or conventional anterior-posterior/posterior-anterior (AP/PA) beams using non-irradiated rats as controls (n = 15/group, n total  = 90). Tumors were assigned to volumes receiving 90-107%, 50-90%, 5-50%, and <5% of the target dose and characterized by histology and loss-of-heterozygosity (LOH). Irradiated rats predominantly developed lymphomas and sarcomas in areas receiving 50-107% (n = 26) rather than 5-50% (n = 7) of the target dose. Latency was significantly shortened only after 3 × 8 Gy vs. controls (p < 0.0001). The frequency (14/28 vs. 19/29; p = 0.29) and latency (218 vs. 189 days; p = 0.17) of radiation-associated tumors were similar after VMAT vs. AP/PA. LOH was strongly associated with sarcoma but not with treatment. The results do not support the hypothesis that IMRT increases the risk of second cancer. Thus the current practice of withholding dose-sparing IMRT from young patients may need to be re-evaluated.

Background and Purpose: In this retrospective treatment planning study, the effect of a uniform and non-uniform planning target volume (PTV) dose coverage as well as a coplanar and non-coplanar volumetric modulated arc therapy (VMAT) delivery approach for lung stereotactic body radiation therapy (SBRT) in deep inspiration breath-hold (DIBH) were compared., Materials and Methods: For 46 patients with lesions in the peripheral lungs, three different treatment plans were generated: First, a coplanar 220° VMAT sequence with a uniform PTV dose prescription (UC). Second, a coplanar 220° VMAT treatment plan with a non-uniform dose distribution in the PTV (nUC). Third, a non-coplanar VMAT dose delivery with four couch angles (0°, ±35°, 90°) and a non-uniform prescription (nUnC) was used. All treatment plans were optimized for pareto-optimality with respect to PTV coverage and ipsilateral lung dose. Treatment sequences were delivered on a flattening-filter-free linear accelerator and beam-on times were recorded. Dosimetric comparison between the three techniques was performed., Results: For the three scenarios (UC, nUC, nUnC), median gross tumor volume (GTV) doses were 63.4 ± 2.5, 74.4 ± 3.6, and 77.9 ± 3.8 Gy, and ipsilateral V10Gy lung volumes were 15.7 ± 6.1, 13.9 ± 4.7, and 12.0 ± 5.1%, respectively. Normal tissue complication probability of the ipsilateral lung was 3.9, 3.1, and 2.8%, respectively. The number of monitor units were 5141 ± 1174, 4104 ± 786, and 3657 ± 710 MU and the corresponding beam-on times were 177 ± 54, 143 ± 29, and 148 ± 26 s., Conclusion: For SBRT treatments in DIBH, a non-uniform dose prescription in the PTV, combined with a non-coplanar VMAT arc arrangement, significantly spares the ipsilateral lung while increasing dose to the GTV without major treatment time increase.

Background: This treatment planning study analyzes dose coverage and dose to organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) of rectal cancer and compares prone vs. supine positioning as well as the effect of dose optimization for the small bowel (SB) by additional dose constraints in the inverse planning process., Patients and Methods: Based on the CT datasets of ten male patients in both prone and supine position, a total of four different IMRT plans were created for each patient. OAR were defined as the SB, bladder, and femoral heads. In half of the plans, two additional SB cost functions were used in the inverse planning process., Results: There was a statistically significant dose reduction for the SB in prone position of up to 41% in the high and intermediate dose region, compared with the supine position. Furthermore, the femoral heads showed a significant dose reduction in prone position in the low dose region. Regarding the additional active SB constraints, the dose in the high dose region of the SB was significantly reduced by up to 14% with the additional cost functions. There were no significant differences in the dose distribution of the planning target volume (PTV) and the bladder., Conclusion: Prone positioning can significantly reduce dose to the SB in IMRT for rectal cancer and therefore should not only be used in 3D conformal radiotherapy but also in IMRT of rectal cancer. Further protection of the SB can be achieved by additional dose constraints in inverse planning without jeopardizing the homogeneity of the PTV.

Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Due to the potentially periodic collimator dynamic in volumetric modulated arc therapy (VMAT) dose deliveries with the sweeping-window arc therapy (SWAT) technique, additional manifestations of dosimetric deviations in the presence of intrafractional motion may occur. With a fast multileaf collimator (MLC), and a flattening filter free dose delivery, treatment times close to 60 s per fraction are clinical reality. For these treatment sequences, the human breathing period can be close to the collimator sweeping period. Compared to a random arrangement of the segments, this will cause a further degradation of the dose homogeneity., Methods: Fifty VMAT sequences of potentially moving target volumes were delivered on a two dimensional ionization chamber array. In order to detect interplay effects along all three coordinate axes, time resolved measurements were performed twice--with the detector aligned in vertical (V) or horizontal (H) orientation. All dose matrices were then moved within a simulation software by a time-dependent motion vector. The minimum relative equivalent uniform dose EUDr,m for all breathing starting phases was determined for each amplitude and period. Furthermore, an estimation of periods with minimum EUD was performed. Additionally, LINAC logfiles were recorded during plan delivery. The MLC, jaw, gantry angle, and monitor unit settings were continuously saved and used to calculate the correlation coefficient between the target motion and the dose weighed collimator motion component for each direction (CC, LR, AP) separately., Results: The resulting EUDr,m were EUDr,m(CCV) = (98.3 ± 0.6)%, EUDr,m(CCH) = (98.6 ± 0.5)%, EUDr,m(APV) = (97.7 ± 0.9)%, and EUDr,m(LRH) = (97.8 ± 0.9)%. The overall minimum relative EUD observed for 360(∘) arc midventilation treatments was 94.6%. The treatment plan with the shortest period and a minimum relative EUD of less than 97% was found at T = 6.1 s. For a partial 120(∘) arc, an EUDr,m = 92.0% was found. In all cases, a correlation coefficient above 0.5 corresponded to a minimum in EUD., Conclusions: With the advent of fast VMAT delivery techniques, nonrobust treatment sequences for human breathing patterns can be generated. These sequences are characterized by a large correlation coefficient between a target motion component and the corresponding collimator dynamic. By iteratively decreasing the maximum allowed dose rate, a low correlation coefficient and consequentially a robust treatment sequence are ensured.

Background and Purpose: Volumetric modulated arc therapy (VMAT) has the potential to deliver dose distributions comparable to the established intensity-modulated radiotherapy techniques for a multitude of target paradigms. Prior to implementing VMAT into their clinical routine in December 2008, the authors evaluated the dose calculation/delivery accuracy of 24 sample VMAT plans (prostate and anal cancer target paradigms) with film and ionization dosimetry. After the start of the clinical program, in vivo measurements with a rectal probe were performed., Material and Methods: The VMAT plans were generated by the treatment-planning system (TPS) ERGO++ (Elekta, Crawley, UK) and transferred to a phantom. Film dosimetry was performed with Kodak EDR2 films, and evaluated with dose profiles and gamma-index analysis. Appropriate ionization chambers were used for absolute dose measurements in the phantom and for in vivo measurements. The ionization chamber was used with localization of the measurement volume based on positioning cone-beam computed tomography., Results: Plans were transferred from ERGO++ to the record and verify (R&V) system/linear accelerator (linac). The absolute dose deviations recorded with the ionization chamber were 1.74% +/- 1.62% across both indications. The gamma-index analysis of the film dosimetry showed no deviation > 3%/3 mm in the high-dose region. On in vivo measurements, a deviation between calculation and measurement of 2.09% +/- 2.4% was recorded, when the chamber was successfully positioned in the high-dose region., Conclusion: VMAT plans can be planned and treated reproducibly in high quality after the commissioning of the complete delivery chain consisting of TPS, R&V system and linac. The results of the individual plan verification meet the commonly accepted requirements. The first in vivo measurements confirm the reproducible precision of the delivered dose during clinical treatments.